Human fetal mesenchymal stem cells as vehicles for gene delivery

Chan, Jerry, O’Donoghue, Keelin, de la Fuente, Josu, Roberts, Irene A., Kumar, Sailesh, Morgan, Jennifer E. and Fisk, Nicholas M. (2005) Human fetal mesenchymal stem cells as vehicles for gene delivery. Stem Cells, 23 1: 93-102. doi:10.1634/stemcells.2004-0138


Author Chan, Jerry
O’Donoghue, Keelin
de la Fuente, Josu
Roberts, Irene A.
Kumar, Sailesh
Morgan, Jennifer E.
Fisk, Nicholas M.
Title Human fetal mesenchymal stem cells as vehicles for gene delivery
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2005-01-01
Year available 2005
Sub-type Article (original research)
DOI 10.1634/stemcells.2004-0138
Open Access Status Not yet assessed
Volume 23
Issue 1
Start page 93
End page 102
Total pages 10
Place of publication Durham, NC, U.S.A
Publisher Wiley-Blackwell and AlphaMed Press
Language eng
Subject 111401 Foetal Development and Medicine
111402 Obstetrics and Gynaecology
1114 Paediatrics and Reproductive Medicine
Abstract First-trimester fetal blood contains a readily expandable population of stem cells, human fetal mesenchymal stem cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation of hfMSCs after transduction with onco-retroviral and lentiviral vectors. After transduction with either a MoMuLV retrovirus or an HIV-1-based lentiviral vector carrying the beta-galactosidase and green fluorescent reporter gene, respectively, transgene expression, self-renewal, and differentiation capabilities were assessed 2 and 14 weeks later. Transduction with the lentiviral vector resulted in higher efficiencies than with the MoMuLV-based vector (mean, 97.7 +/- 1.4% versus 80.2 +/- 5.4%; p = .02). Transgene expression was maintained with lentiviral-transduced cells (94.6 +/- 2.6%) but decreased over 14 weeks in culture with onco-retroviral-transduced cells (48.3 +/- 3.9%). The self-renewal capability of these cells and their ability to undergo osteogenic, adipogenic, and myogenic differentiation was unimpaired after transduction with either vector. Finally, clonal expansion of lentivirally modified cells was expanded over 20 population doublings with maintenance of multilineage differentiation capacity. These results suggest that hfMSCs may be suitable targets for ex vivo genetic manipulation with onco-retroviral or lentiviral vectors without affecting their stem cell properties.
Formatted abstract
First-trimester fetal blood contains a readily expandable population of stem cells, human fetal mesenchymal stem cells (hfMSCs), which might be exploited for autologous intrauterine gene therapy. We investigated the self-renewal and differentiation of hfMSCs after transduction with onco-retroviral and lentiviral vectors. After transduction with either a MoMuLV retrovirus or an HIV-1-based lentiviral vector carrying the ß-galactosidase and green fluorescent reporter gene, respectively, transgene expression, self-renewal, and differentiation capabilities were assessed 2 and 14 weeks later. Transduction with the lentiviral vector resulted in higher efficiencies than with the MoMuLV-based vector (mean, 97.7 ± 1.4% versus 80.2 ± 5.4%; p = .02). Transgene expression was maintained with lentiviral-transduced cells (94.6 ± 2.6%) but decreased over 14 weeks in culture with onco-retroviral-transduced cells (48.3 ± 3.9%). The self-renewal capability of these cells and their ability to undergo osteogenic, adipogenic, and myogenic differentiation was unimpaired after transduction with either vector. Finally, clonal expansion of lentivirally modified cells was expanded over 20 population doublings with maintenance of multiline age differentiation capacity. These results suggest that hfMSCs may be suitable targets for ex vivo genetic manipulation with onco-retroviral or lentiviral vectors without affecting their stem cell properties.
Copyright © 2010 AlphaMed Press.

Keyword Mesenchymal Stem Cells
Lentivirus
Retrovirus
Gene Therapy
Fetal
Q-Index Code C1
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 108 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 20 Mar 2009, 22:09:05 EST by Maria Campbell on behalf of Faculty Of Health Sciences